The long range objective of this project is to apply the techniques of biochemistry to investigate how genes of the nervous system are expressed and regulated. The nervous system is composed of many neurons which interconnect with one another in a precise manner. The diversity of neurons and the nature of their interactions suggest that specific genes or sets of genes are activated in some neurons and not in others. The autonomic nervous system affords a particularly suitable approach to analyzing specific gene expression. The adrenal medulla is part of the autonomic nervous system which is embryologically derived from neurons tissue and which is analogous to postganglionic neurons. The adrenal medulla is a major site of catecholamine biosynthesis as well as the site for synthesis of neuropeptides. One of the specific aims of this proposal is to develop a better understanding of the molecular events regulating the rate controlling enzyme in catecholamine biosynthesis (tyrosine hydroxylase) and the newly discovered peptide which has been named neuropeptide Y. The brain also synthesizes numerous classical neurotransmitters and neuropeptides. Two of the major neuropeptides found in the brain are neuropeptide Y and cholecystokinin. The tools of molecular biology will be used t develop a better understanding of how the gene(s) encoding cholecystokinin are controlled and modulated during development. The information obtained from these studies should also suggest structures for the precursors to human and rat cholecystokinin(s) and potential sties of post-translational processing.